Antioxidant, Analgesic and CNS Depressant Activities of Commelina diffusa Burm. f.

Commelina diffusa Burm. f. is a member of Commelinaceae family, which is widely grown in crop land and treated as a weed. This plant has several important medicinal properties which have not been studied extensively. In this study, the crude powder of C. diffusa whole plant was extracted with 95% ethanol and different solvent fractions (n-hexane, chloroform and methanol) were prepared from the crude extract by solvent-solvent partitioning. All these plant samples were subjected to bioassays for evaluating the antioxidant, central analgesic, peripheral analgesic and CNS depressant activities. The crude extract and its methanol soluble fraction showed mild free DPPH scavenging property with IC50 values of 98.49- and 84.77-μg/ml, respectively as compared to the standard ascorbic acid (IC50 = 2.67 μg/ml). In the analgesic activity test, the n-hexane fraction of C. diffusa at doses of 200- and 400-mg/kg body weight exhibited significant (p<0.05) central analgesic activity (tail flick test) in mice. Similarly, all the test samples showed statistically significant (p<0.05) reduction in abdominal writhing induced by acetic acid. C. diffusa showed significant CNS depressant activity which was measured by ‘open field test’ and ‘hole cross test’. Considering the potential bioactivities, the plant materials can be further studied elaborately to explore the activities of the purified compounds to aid in future drug development. Dhaka Univ. J. Pharm. Sci. 20(2): 159-166, 2021 (December)

CNS Depressant and Analgesic Activities of Thysanolaena maxima Roxb. Available in Bangladesh

In Bangladesh, numerous tribal people of Chittagong Hill Tracts have been using different parts of Thysanolaena maxima Roxb. for many years. The present study was designed to investigate CNS depressant and analgesic activities of methanol extract of the aerial parts of the plant in mice models. CNS depressant activity of the crude extract (200 and 400 mg/kg) was evaluated using open field, hole cross and thiopental-induced sleeping time tests using diazepam as the standard. Analgesic activity was determined using acetic acid-induced writhing and hot plate tests using diclofenac sodium as the standard. The extract showed dose dependent suppression of locomotion in open field and hole cross tests and exerted sedative action in thiopental induced sleeping time. In the open field and the hole-cross tests, maximum CNS depressant activity was observed at 90 min after administration of extract and the standard drug. The extract significantly induced the onset of sleep and prolonged the sleeping time in thiopental induced sleeping test compared to the control group. The extract produced significant (p < 0.05) analgesic activity by inhibiting writhing by 41.89% and 60.81%, at doses of 200 and 400 mg/kg body weight, respectively, which was comparable to the inhibition of diclofenac sodium (73.64%). Additionally, in hot plate test, the extract exhibited a significant (p < 0.05) increase in pain threshold in a dose dependent manner. The findings of the study are encouraging and demands further investigation of other bioactivities with isolation of pure compounds. Dhaka Univ. J. Pharm. Sci. 20(2): 227-233, 2021 (December)

Central nervous system depressant activity of fractions of Globimetula braunii Engl. (Loranthaceae) growing on Terminalia catappa L. (Combretaceae) and isolation of lupeol

Globimetula braunii is a parasitic plant belonging to the family Loranthaceae. Traditionally, the plant has been reported to be used in the treatment of insomnia. The study was carried out to investigate the central nervous system (CNS) depressant activity of the fractions of Globimetula braunii growing on Terminalia catappa and to isolate the phytochemical compound(s) present in the most active fraction. The CNS depressant activity of all the fractions was investigated using diazepam induced sleep. The most active fraction was further subjected to the hole board test and beam walk assay. The chromatographic technique was used for the isolation of phytochemical compound. Hexane fraction significantly (p<0.05) reduced latency to sleep and prolonged the sleeping time. Both chloroform and ethylacetate fractions at highest and median doses showed significant increase in the duration of sleep compared to normal saline. The n-butanol fraction at all doses tested do not have any effect on time of onset and duration of sleep when compared with normal saline treated group. Hexane fraction significantly (p<0.05) decreased the number of head dip in a dose dependent manner and delayed the time to reach the goal box compared to normal saline treated group. Lupeol was isolated from n-hexane fraction.

Trends in drug poisoning deaths, by sex, in Ireland: a repeated cross-sectional study from 2004 to 2017

ObjectiveTo examine sex differences in age-standardised rates (ASR) of overall and drug-specific drug poisoning deaths in Ireland between 2004 and 2017.DesignRepeated cross-sectional study.SettingDrug poisoning deaths in Ireland.ParticipantsNational Drug-Related Deaths Index and pharmacy claims database (Primary Care Reimbursement Service-General Medical Services) data from 2004 to 2017.Outcome measuresThe primary outcome was trends in drug poisoning death rates by sex. The secondary outcomes were trends in drug poisoning death rates involving (1) any CNS (Central Nervous System) depressants, (2) ≥2 CNS depressants and (3) specific drugs/drug classes (eg, prescription opioids, benzodiazepines, antidepressants, alcohol, cocaine and heroin) by sex. Joinpoint regression was used to examine trends, stratified by sex, in the ASR of drug poisoning deaths (2004–2017), change points over time and average annual percentage changes (AAPCs) with 95% CI.ResultsIncreased ASR for all drug poisoning deaths from 6.86 (95% CI 6.01 to 7.72) per 100 000 in 2004 to 8.08 (95% CI 7.25 to 8.91) per 100 000 in 2017 was mainly driven by increasing deaths among men (AAPC 2.6%, 95% CI 0.2 to 5.1), with no significant change observed among women. Deaths involving ≥2 CNS depressants increased for both men (AAPC 5.6%, 95% CI 2.4 to 8.8) and women (AAPC 4.0%, 95% CI 1.1 to 6.9). Drugs with the highest significant AAPC increases for men were cocaine (7.7%, 95% CI 2.2 to 13.6), benzodiazepines (7.2%, 95% CI 2.9 to 11.6), antidepressants (6.1%, 95% CI 2.4 to 10.0) and prescription opioids (3.5%, 95% CI 1.6 to 5.5). For women, the highest AAPC was for antidepressants (4.2%, 95% CI 0.2 to 8.3), benzodiazepines (3.3%, 95% CI 0.1 to 6.5) and prescription opioids (3.0%, 95% CI 0.7 to 5.3).ConclusionDrugs implicated in drug poisoning deaths vary by sex. Policy response should include prescription monitoring programmes and practical harm reduction information on polydrug use, especially CNS depressant drugs.

Pharmacological Importance of Saraca asoca: A Review

Ayurveda is a traditional medicinal system which has been used consistently. Asoka is one of India's most holy and legendary trees. Ashoka, also known as Saraca asoca (Roxb.) Wilde, is an indigenous plant that belongs to the Caesalpiniaceae subfamily of the Legume. It is an evergreen tree of medium size. The objective of this review is to provide detailed description of botany, phytochemicals, medicinal value and pharmacological activity. Saraca asoca was reported to be comprising phytoconstituents, such as Flavonoids, Steroids, Glycosides, Saponins, Carbohydrates, Proteins as well as many Pharmacologic activities such as anti-diabetic, CNS depressant, anti-helminthic, cardio protective, anti-bacterial, anti-menorrhagic, anti-hyperglycaemic and anti-oxidant activities, anti-cancer activities.

Pharmacological evaluation for Anti-Anxiety and CNS depressant activity of hydro-alcoholic leaves extract of Pongamia pinnata

The aim of this study was to assess the anti-anxiety and CNS depressant properties of hydro-alcoholic extract of Pongamia pinnata leaves (HALEPP). Standard methods were used to screen the HALEPP's phytochemicals, which showed that the extract contains Flavones, alkaloids, glycosides, proteins and amino acids, gum and mucilage as well as flavonoids, saponins, and steroid hormones. Even at the dose level of 1000 mg/kg body weight, the HALEPP showed no signs of toxicity or mortality in the acute toxicity report. The anti-anxiety behaviour of was studied using light and dark model methods in rats. The CNS depressant action was studied using the extract and actophotometer (Rolex) in rats. The research group (HALEPP 200 gm/kg treated) animals displayed strong anti-anxiety and CNS depressant behaviour similar to the control group (diazepam treated) animals in the current study. The study's findings suggest that the hydro-alcoholic Pongamia pinnata leaf extract has strong anti-anxiety and CNS depressant properties. Keywords: Pongamia pinnata, Anti-Anxiety & CNS depressant

Investigation of Analgesic, Anti-Inflammatory, Hypoglycaemic, Neuropharmacological and Cytotoxic Properties of Clerodendrum viscosum (Leaves)

Clerodendrum viscosum (CV) has been used traditionally to treat medical problems like asthma, ulcer, inflammation, pyrexia, diabetes, malaria, skin diseases, snakebite and tumor by folk practitioners. The present study evaluated the analgesic, antiinflammatory, neuropharmacological and cytotoxic properties C. viscosum (leaves) in rodents. Swiss albino mice of either sex weighing 25-30 gm and SD rats (150-180 mg) were divided into control (DW), standard (model specific) as well as test groups (n=6). Analgesic potential was evaluated using acetic acid-induced writhing and formalin induced pawlicking test. Anti-inflammatory properties were evaluated by xylene and croton oil induced ear edema test. Glucose tolerance was evaluated by OGTT in normal rats. Pentobarbital induced sleeping time test was applied to assess neuropharmacological activity. Also, Brine shrimp lethality bioassay method was employed for cytotoxicity evaluation. The alcoholic extracts showed significant antinociceptive activity in acetic acid test (p<0.01) and formalin test (p<0.05) at the dose of 1000mg/kg bw. The crude extract reduced inflammation significantly (p<0.01) in both xylene and croton oil induced ear edema test. At the dose of 1000mg/kg it increased glucose tolerance significantly (p<0.05) in normal rats. CV extract significantly (p<0.01) increased sleeping time indicating CNS depressant effect. The extract exhibited a potent cytotoxicity against brine shrimp (LC50=316.23μg/ml). C. viscosum leaves showed analgesic, antiinflammatory, hypoglycemic and CNS depressant effect against experimentally induced model mice. It also possessed cytotoxic properties and further studies are required to evaluate these effects and the potential of the plant.

Essential Oil from the Leaves of Chromolaena odorata, and Sesquiterpene Caryophyllene Oxide Induce Sedative Activity in Mice

Chromolaena odorata (L.) R.M.King & H.Rob. essential oil (COEO) was investigated for its sedative activity in mice. The results showed that COEO significantly reduced mice locomotor activity and the most efficient concentrations were 0.04 and 0.00004 mg/cage (volume of the cage 61.2L). Analysis of chemical composition of the oil indicated that caryophyllene oxide (43.75%) was the major compound and bioactivity-guided fractionation of the oil was performed to isolate the compound responsible for activity. The data clearly identified sesquiterpene caryophyllene oxide as the compound inducing COEO sedative activity and it was effective in decreasing mice locomotor activity by 56% and 57% at 0.0004 and 0.04 mg/cage, respectively. In order to understand the action mechanisms, caryophyllene oxide was tested for its effects on the central nervous system (CNS) by using a caffeine pre-excited mice test and a pentobarbital sleeping-induced test in mice. The results showed that caryophyllene oxide is a potent CNS depressant. Nevertheless, it fails to potentiate the effects of pentobarbital on the GABAergic system, nor did flumazenil, a GABAA receptor antagonist, reversed its effects. It was especially interesting to note that β-caryophyllene, the precursor of caryophyllene oxide, demonstrated a similar pattern of sedative activity, and the present work further extends actual knowledge on these naturally occurring sesquiterpenes. The findings in this study reveal the new activity of caryophyllene oxide as an innovative way to manage sleep and CNS-related disorders, and demonstrates a satisfactory effect of two interesting sesquiterpene compounds on the CNS.

Characterization of hospitalized patients who received naloxone while receiving opioids with or without gabapentinoids

Introduction Gabapentin and pregabalin (gabapentinoids) can be given with opioids for opioid-sparing and adjuvant analgesic effects. In the context of certain comorbidities and high dosages, coadministration of these agents can lead to respiratory depression or oversedation, necessitating naloxone administration. Methods A retrospective chart review from January 2015 to December 2017 was conducted to include patients who received naloxone and opioids with or without gabapentinoids. Exclusion criteria included pregnancy or having received naloxone in the emergency department, intensive care, or pediatrics units. The primary outcome was to characterize differences between groups regarding comorbidities, history of renal or hepatic dysfunction, history of SUD, opioid tolerance, initiation and dose appropriateness of gabapentinoids, and dose intensity of gabapentinoids and opioids. Secondary outcomes were concomitant CNS depressant use and naloxone episodes for documented respiratory depression. Results Of 126 patients who met inclusion criteria, 36 received opioids and gabapentinoids (gabapentinoid group) and 90 received opioids alone (nongabapentinoid group). There were 136 naloxone episodes between the 2 groups. More than 50% of the naloxone episodes in the gabapentinoid group involved opioids of at least 90 oral morphine mg equivalents. Respiratory depression accounted for 39% and 15.8% of the naloxone episodes in the gabapentinoid and nongabapentinoid groups, respectively. Discussion There may be increased naloxone episodes among patients receiving opioids and gabapentinoids. Future studies are needed to evaluate the incremental risk of respiratory depression and oversedation as it pertains to concomitant medication administration and patient-specific factors.